1. Field
This invention is in the field of methods for diagnosis and appraisal of treatment of disease conditions.
2. State of the Art
Breast cancer, lung cancer, colon cancers, pancreatic cancers and related pre-cancer growths are a very serious concern for the citizens of the United States and the world. The morbidity and mortality from these conditions is source of considerable physical and economic distress to the populations of this country and countries of the world. Jemal A et al. Cancer Statistics 2004, CA Cancer J Clin, 2005 54(1): 118-129. The treatment of growths, cancers and other disease conditions of organs often requires their replacement with a transplanted organ from another person or mammalian creature. The pre-transplantation evaluation of the donor and the recipient of the transplanted organ as well as the post transplant evaluation of the recipient for rejection of the transplant and the development of other diseases related and unrelated to the transplantation treatment is also a daunting task. There is clearly a need for better markers to indicate the state of disease and growing tumors, as well as the pre and post transplant clinical status of donor and recipient. If growths of the breast, lung, pancreas and colon are detected sooner with better markers the chances of successful cure are greatly improved.
Since the dividing time of the cells in most growths are several days, the growth usually has been present for many months or years before it is detectable by present imaging and other diagnostic methods. Pathway markers have not as yet proved successful in the early diagnosis of most of these growths with a high degree of specificity or sensitivity.
With the development of tumors, dendritic cells or macrophages note new growth, whether of genetic or epigenetic origin, by recognizing the altered proteins, often presented on the cancer cell's surface through their receptor channels. The dendritic cells convey these altered protein changes to the lymphocytes with the addition of major histocompatibility complexes. This includes T. lymphocytes CD8 with HCS I and CD4 with HCS II. The B lymphocytes are subsequently programmed by the recognizing T lymphocyte. Zeng, G., MHC Class II-Restricted Tumor Antigens Recognized by CD4+ T Cells: New Strategies for Cancer Vaccine Design. J Immunother, 2001. 24(3): p. 195-204; Jonuleit, H., et al., Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med, 2001. 193(11): p. 1285-94; Serbina N. V., Pamer E. G. Giving Credit Where Credit Is Due. Science, 2003, 301:1856-1857; and Baxevanis, C. N., et al., Tumor-specific CD4+ T lymphocytes from cancer patients are required for optimal induction of cytotoxic T cells against the autologous tumor. J Immunol, 2000. 164(7): p. 3902-12. Through this mechanism, the lymphocytes specifically recognize the new growth and program specifically against it, sending tumor infiltrating lymphocytes or TIL cells to the new growth. These TIL cells may decrease in the area of the tumor as tolerance for the tumor develops. Ryschich, E., et al., Transformation of the microvascular system during multistage tumorigenesis. Int J Cancer, 2002. 97(6): p. 719-25. It has been shown that the CD4-CD25 T lymphocytes contribute to tolerance of developing cancer. Liyanage, U. K., et al., Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol, 2002. 169(5): p. 2756-61. The use of peripheral blood lymphocytes for diagnosis of certain diseases have been proposed and described in Hong M H, X. X., Mai H Q, Cao S M Min H Q, Analysis of gene expression patterns of periphery lymphocytes in patients with nasopharyngeal carcinoma. Ai Zheng, 2002. 21(1): p. 21-4; Xu T et al Microarray analysis reveals differences in gene expression of circulating CD8+ T cells in melanoma patients and healthy donors. Cancer Res. 2004 May 15; 64(10):3661-7; Thomas A M et al. Mesothelin-specific CD8(+) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J. Exp Med. 2004 Aug. 2; 200(3): 297-306; and McLaren P J et al Antigen-specific gene expression profiles of peripheral blood mononuclear cells do not reflect those of T-lymphocyte subsets. Clin Diagn Lab Immunol. 2004 September; 11(5):977-82. Twine & Burczynski. Twine N C, et al. Disease-associated expression profiles in peripheral blood mononuclear cells from patients with advanced renal cell carcinoma. Cancer Res. 2003 Sep. 15; 63(18):6069-75. Burczynski M E, Twine N C et. al. Transcriptional profiles in peripheral blood mononuclear cells prognostic of clinical outcomes in patients with advanced renal cell carcinoma. Clinical Cancer Res. 2005 Feb. 1; 11(3):1181-9.